APOBEC3A/B deletion polymorphism and endometrial cancer risk

Area of Science:

• Genetics
• Cancer Research
• Epidemiology

Background:

• A common 30 kb deletion in APOBEC3A and APOBEC3B genes is associated with increased APOBEC activity and cancer mutational signatures.
• The role of this deletion in cancer risk is currently debated.

Purpose of the Study:

• To investigate the association between the APOBEC3A/B deletion and endometrial cancer risk.
• To assess the deletion's role as a potential cancer risk factor.

Main Methods:

• Genotyping of the APOBEC3A/B deletion in 1,470 Norwegian endometrial cancer cases and 1,918 controls.
• Analysis of SNP rs12628403 genotypes in a large Caucasian GWAS dataset (4,274 cases, 18,125 controls) via the ECAC consortium.

Main Results:

• The APOBEC3A/B deletion was significantly associated with reduced endometrial cancer risk in Norwegian women (OR=0.75, p=0.003).
• A similar risk reduction was observed in endometrioid endometrial cancer (OR=0.64, p=3.6×10⁻⁵).
• Risk reduction was most pronounced in women aged 50-60 (OR=0.51, p=0.002).
• While trends suggested reduced risk in other Caucasian populations, the overall ECAC consortium results were not statistically significant.

Conclusions:

• The APOBEC3A/B deletion polymorphism is associated with a decreased risk of endometrial cancer in the Norwegian population.
• The findings highlight a potential protective genetic factor for endometrial cancer in specific populations.